Liang Winnie H, Li Qiaochu, Rifat Faysal K M, King Stephen J, Gopinathan Ajay, Xu Jing
Department of Physics, School of Natural Sciences, University of California, Merced, California.
Burnett School of Biomedical Sciences, University of Central Florida, Orlando, Florida.
Biophys J. 2016 May 24;110(10):2229-40. doi: 10.1016/j.bpj.2016.04.029.
Microtubules are protein polymers that form "molecular highways" for long-range transport within living cells. Molecular motors actively step along microtubules to shuttle cellular materials between the nucleus and the cell periphery; this transport is critical for the survival and health of all eukaryotic cells. Structural defects in microtubules exist, but whether these defects impact molecular motor-based transport remains unknown. Here, we report a new, to our knowledge, approach that allowed us to directly investigate the impact of such defects. Using a modified optical-trapping method, we examined the group function of a major molecular motor, conventional kinesin, when transporting cargos along individual microtubules. We found that microtubule defects influence kinesin-based transport in vitro. The effects depend on motor number: cargos driven by a few motors tended to unbind prematurely from the microtubule, whereas cargos driven by more motors tended to pause. To our knowledge, our study provides the first direct link between microtubule defects and kinesin function. The effects uncovered in our study may have physiological relevance in vivo.
微管是一种蛋白质聚合物，在活细胞内形成用于远程运输的“分子高速公路”。分子马达沿着微管积极移动，在细胞核和细胞周边之间穿梭细胞物质；这种运输对所有真核细胞的存活和健康至关重要。微管存在结构缺陷，但这些缺陷是否会影响基于分子马达的运输仍不清楚。在此，据我们所知，我们报告了一种新方法，使我们能够直接研究此类缺陷的影响。使用改进的光镊方法，我们研究了主要分子马达——传统驱动蛋白在沿着单个微管运输货物时的群体功能。我们发现微管缺陷在体外影响基于驱动蛋白的运输。其影响取决于马达数量：由少数马达驱动的货物往往会过早地从微管上脱离，而由更多马达驱动的货物则往往会暂停。据我们所知，我们的研究首次建立了微管缺陷与驱动蛋白功能之间的直接联系。我们研究中发现的这些影响可能在体内具有生理相关性。
